CA1256867A - Derives de 3-piperidinyl-1,2-benzisoxazol et de 3-piperidinyl-1,2-benzisothiazol - Google Patents

Derives de 3-piperidinyl-1,2-benzisoxazol et de 3-piperidinyl-1,2-benzisothiazol

Info

Publication number: CA1256867A
Authority: CA; Canada
Prior art keywords: formula; hydrogen; halo; alkyl; radical
Prior art date: 1985-03-27
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA000504409A

Other languages

English (en)

Inventor

Ludo E. J. Kennis

Jan Vandenberk

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Janssen Pharmaceutica NV

Original Assignee

Janssen Pharmaceutica NV

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1985-03-27

Filing date

1986-03-18

Publication date

1989-07-04

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26664247&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA1256867(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1986-03-18 Application filed by Janssen Pharmaceutica NV filed Critical Janssen Pharmaceutica NV

1989-07-04 Application granted granted Critical

1989-07-04 Publication of CA1256867A publication Critical patent/CA1256867A/fr

Status Expired legal-status Critical Current

Links

-1 1,2-benzisoxazol-3-yl Chemical class 0.000 title claims abstract description 45
150000003839 salts Chemical class 0.000 claims abstract description 30
239000002253 acid Substances 0.000 claims abstract description 25
238000011282 treatment Methods 0.000 claims abstract description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 99
239000001257 hydrogen Substances 0.000 claims description 99
150000001875 compounds Chemical class 0.000 claims description 94
150000002431 hydrogen Chemical class 0.000 claims description 47
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
125000000217 alkyl group Chemical group 0.000 claims description 29
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 25
238000000034 method Methods 0.000 claims description 25
125000003545 alkoxy group Chemical group 0.000 claims description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 13
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 11
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 11
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
239000012442 inert solvent Substances 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 9
208000028017 Psychotic disease Diseases 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 8
239000003153 chemical reaction reagent Substances 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 6
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 5
239000003513 alkali Substances 0.000 claims description 5
239000012458 free base Substances 0.000 claims description 5
NNAGVKRGLGDZRM-UHFFFAOYSA-N 3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2-methylpyrido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4C=CC=CC4=NC=3C)=NOC2=C1 NNAGVKRGLGDZRM-UHFFFAOYSA-N 0.000 claims description 4
MRMGJMGHPJZSAE-UHFFFAOYSA-N 6-fluoro-3-piperidin-4-yl-1,2-benzoxazole Chemical compound N=1OC2=CC(F)=CC=C2C=1C1CCNCC1 MRMGJMGHPJZSAE-UHFFFAOYSA-N 0.000 claims description 4
239000004202 carbamide Substances 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
231100000252 nontoxic Toxicity 0.000 claims description 4
230000003000 nontoxic effect Effects 0.000 claims description 4
239000012948 isocyanate Substances 0.000 claims description 3
150000002513 isocyanates Chemical class 0.000 claims description 3
LFTGLYCNMGGMKL-UHFFFAOYSA-N 3-(2-chloroethyl)-2-methylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=CC=CN2C(=O)C(CCCl)=C(C)N=C21 LFTGLYCNMGGMKL-UHFFFAOYSA-N 0.000 claims description 2
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 2
150000002540 isothiocyanates Chemical class 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 38
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 34
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 7
RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 claims 3
CMWCQQUYLPYOMY-UHFFFAOYSA-N 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound C1CCCN2C(=O)C(CCCl)=C(C)N=C21 CMWCQQUYLPYOMY-UHFFFAOYSA-N 0.000 claims 1
241000352333 Amegilla alpha Species 0.000 claims 1
150000002825 nitriles Chemical class 0.000 claims 1
239000000126 substance Substances 0.000 claims 1
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 6
229940076279 serotonin Drugs 0.000 abstract description 3
230000000561 anti-psychotic effect Effects 0.000 abstract description 2
JGBDELPHTHPTEY-UHFFFAOYSA-N 3-piperidin-1-yl-1,2-benzothiazole Chemical class C1CCCCN1C1=NSC2=CC=CC=C12 JGBDELPHTHPTEY-UHFFFAOYSA-N 0.000 abstract 1
FFESGTAUFAZQRI-UHFFFAOYSA-N 3-piperidin-1-yl-1,2-benzoxazole Chemical class C1CCCCN1C1=NOC2=CC=CC=C12 FFESGTAUFAZQRI-UHFFFAOYSA-N 0.000 abstract 1
239000000203 mixture Substances 0.000 description 32
125000005843 halogen group Chemical group 0.000 description 25
239000000243 solution Substances 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
239000000543 intermediate Substances 0.000 description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
150000003254 radicals Chemical class 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
239000000047 product Substances 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
238000002360 preparation method Methods 0.000 description 8
238000003756 stirring Methods 0.000 description 8
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
238000001816 cooling Methods 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000003480 eluent Substances 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 5
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
229960002748 norepinephrine Drugs 0.000 description 5
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 5
238000007363 ring formation reaction Methods 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
241000700159 Rattus Species 0.000 description 4
229960004046 apomorphine Drugs 0.000 description 4
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000000725 suspension Substances 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
239000000654 additive Substances 0.000 description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
239000002585 base Substances 0.000 description 3
238000009835 boiling Methods 0.000 description 3
229960001701 chloroform Drugs 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
150000002923 oximes Chemical class 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000007858 starting material Substances 0.000 description 3
WQJPGQDCLBMXMH-UHFFFAOYSA-N (2,4-difluorophenyl)-piperidin-4-ylmethanone Chemical compound FC1=CC(F)=CC=C1C(=O)C1CCNCC1 WQJPGQDCLBMXMH-UHFFFAOYSA-N 0.000 description 2
SKYZYDSNJIOXRL-BTQNPOSSSA-N (6ar)-6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-10,11-diol;hydrochloride Chemical compound Cl.C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 SKYZYDSNJIOXRL-BTQNPOSSSA-N 0.000 description 2
YXTROGRGRSPWKL-UHFFFAOYSA-N 1-benzoylpiperidine Chemical compound C=1C=CC=CC=1C(=O)N1CCCCC1 YXTROGRGRSPWKL-UHFFFAOYSA-N 0.000 description 2
PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
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241001024304 Mino Species 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
229960003990 apomorphine hydrochloride Drugs 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
239000008103 glucose Substances 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
125000002346 iodo group Chemical group I* 0.000 description 2
235000014655 lactic acid Nutrition 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000843 powder Substances 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
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239000000376 reactant Substances 0.000 description 2
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
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QPJONRGTWKXJLG-UHFFFAOYSA-N (2,4-difluorophenyl)-piperidin-4-ylmethanone;hydrochloride Chemical compound Cl.FC1=CC(F)=CC=C1C(=O)C1CCNCC1 QPJONRGTWKXJLG-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D497/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D497/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Hematology (AREA)
Anesthesiology (AREA)
Diabetes (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Hydrogenated Pyridines (AREA)

CA000504409A 1985-03-27 1986-03-18 Derives de 3-piperidinyl-1,2-benzisoxazol et de 3-piperidinyl-1,2-benzisothiazol Expired CA1256867A (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US71706785A	1985-03-27	1985-03-27
US717,067		1985-03-27
SG119294A SG119294G (en)	1985-03-27	1994-08-20	1,2-benzisoxazol-3-yl and 1,2-benzisothiazol-3-yl derivatives

Publications (1)

Publication Number	Publication Date
CA1256867A true CA1256867A (fr)	1989-07-04

Family

ID=26664247

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000504409A Expired CA1256867A (fr)	1985-03-27	1986-03-18	Derives de 3-piperidinyl-1,2-benzisoxazol et de 3-piperidinyl-1,2-benzisothiazol

Country Status (15)

Country	Link
US (1)	US4804663A (fr)
EP (1)	EP0196132B1 (fr)
JP (1)	JPH0613511B2 (fr)
CN (1)	CN1022566C (fr)
AU (1)	AU579232B2 (fr)
BG (1)	BG60432B2 (fr)
CA (1)	CA1256867A (fr)
CY (1)	CY1801A (fr)
DK (1)	DK168537B1 (fr)
HK (1)	HK108794A (fr)
IE (1)	IE58388B1 (fr)
LU (1)	LU88576I2 (fr)
NL (1)	NL940006I2 (fr)
SG (1)	SG119294G (fr)
SU (1)	SU1468419A3 (fr)

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1986
- 1986-02-05 US US06/826,517 patent/US4804663A/en not_active Expired - Lifetime
- 1986-03-05 SU SU864027047A patent/SU1468419A3/ru active
- 1986-03-13 LU LU88576C patent/LU88576I2/fr unknown
- 1986-03-13 EP EP86200400A patent/EP0196132B1/fr not_active Expired - Lifetime
- 1986-03-18 CA CA000504409A patent/CA1256867A/fr not_active Expired
- 1986-03-24 CN CN86101906A patent/CN1022566C/zh not_active Expired - Lifetime
- 1986-03-26 IE IE80186A patent/IE58388B1/en not_active IP Right Cessation
- 1986-03-26 DK DK143986A patent/DK168537B1/da not_active IP Right Cessation
- 1986-03-26 JP JP61066108A patent/JPH0613511B2/ja not_active Expired - Lifetime
- 1986-03-26 AU AU55297/86A patent/AU579232B2/en not_active Expired
1993
- 1993-06-16 BG BG097873A patent/BG60432B2/bg unknown
1994
- 1994-04-11 NL NL940006C patent/NL940006I2/nl unknown
- 1994-08-20 SG SG119294A patent/SG119294G/en unknown
- 1994-10-06 HK HK108794A patent/HK108794A/en not_active IP Right Cessation
1995
- 1995-02-17 CY CY180195A patent/CY1801A/xx unknown

Also Published As

Publication number	Publication date
CY1801A (en)	1995-02-17
NL940006I2 (nl)	1999-09-01
EP0196132A3 (en)	1988-01-20
EP0196132B1 (fr)	1992-08-12
US4804663A (en)	1989-02-14
AU579232B2 (en)	1988-11-17
CN1022566C (zh)	1993-10-27
JPH0613511B2 (ja)	1994-02-23
HK108794A (en)	1994-10-14
SG119294G (en)	1995-03-17
IE58388B1 (en)	1993-09-08
DK143986A (da)	1986-09-28
DK168537B1 (da)	1994-04-18
SU1468419A3 (ru)	1989-03-23
LU88576I2 (fr)	1995-03-21
CN86101906A (zh)	1986-10-01
BG60432B2 (bg)	1995-03-31
DK143986D0 (da)	1986-03-26
EP0196132A2 (fr)	1986-10-01
JPS61221186A (ja)	1986-10-01
IE860801L (en)	1986-09-27
AU5529786A (en)	1986-10-02
NL940006I1 (nl)	1994-05-16

Legal Events

Date	Code	Title	Description
2006-07-04	MKEX	Expiry

Publication	Publication Date	Title
US4804663A (en)	1989-02-14	3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles
CA1257258A (fr)	1989-07-11	N-(heterocyclyle bicyclique)-4-piperidinamines
US4588722A (en)	1986-05-13	N-(4-piperidinyl) bicyclic condensed 2-imidazolamine derivatives
US4443451A (en)	1984-04-17	Bicyclic pyrimidin-5-one derivatives
US5140029A (en)	1992-08-18	2-aminopyrimidinone derivatives
US4957916A (en)	1990-09-18	Antipsychotic 3-piperazinylbenzazole derivatives
US4835161A (en)	1989-05-30	Anti-histaminic compositions containing n-heterocyclyl-4-piperidinamines
EP0353821B1 (fr)	1995-05-10	Dérivés du 3-pipérazinyl-benzazole antipsychotiques
US4695569A (en)	1987-09-22	Bicyclic heterocyclyl containing N-(bicyclic heterocyclyl)-4-piperidinamines
US4548938A (en)	1985-10-22	5-H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one compounds
WO1992006086A1 (fr)	1992-04-16	Nouveaux derives de 4-piperidinylcarbonyle
US5015740A (en)	1991-05-14	Antipsychotic 3-piperazinylbenzazole derivatives
US4529727A (en)	1985-07-16	Pyrimido[2,1-b][1,3]-thiazines
US5217980A (en)	1993-06-08	Oxazolyl and piperidinyl substituted benimidazolyl compounds
EP0357134B1 (fr)	1995-06-28	Dérivés de 3-pipéridinyl-indazole antihypertensifs
US5196425A (en)	1993-03-23	Antihypertensive 3-piperidinyl-indazole derivatives
US5321028A (en)	1994-06-14	Antihypertensive 3-piperidinyl-indazole derivatives
US5284854A (en)	1994-02-08	2-aminopyrimidinone derivatives
US5126339A (en)	1992-06-30	Anti-allergic bicyclic heterocyclyl-containing N-(bicyclic heterocyclyl)-4-piperidinamines
DE3686341T2 (de)	1993-01-14	1,2-benzisoxazol-3-yl- und 1,2-benzisothiazol-3-yl-derivate.
US5025014A (en)	1991-06-18	Bicyclic heterocyclyl containing N-(bicyclic heterocyclyl)-4-piperidinamines as pharmaceuticals
US4888426A (en)	1989-12-19	1-(5-methyl-furan-2-ylmethyl)-N-(4-piperidinyl)imidazo [4,5-6]pyridine-2-amine
SK280125B6 (sk)	1999-08-06	1,2-benzazoly a farmaceutické prostriedky na ich b
IL105594A (en)	1994-10-07	History of 3-piperazinylbenzperazole